Cognitive Deficits Common at Onset of Seizures

Action Points

Explain to interested patients and parents that abnormalities in language, learning, and behavior are often present in children with epilepsy.

Also note that the occurrence of a seizure should prompt testing so that educational interventions can help minimize the cognitive impact of the disease.

Neuropsychological impairments were already present in more than a quarter of intellectually normal children ages 6 to 14 tested within three months of experiencing a first seizure, researchers found.

And up to 40% of those with associated risk factors exhibited neuropsychological deficits, Philip S. Fastenau, PhD, of Case Western Reserve University, and colleagues, reported in the Aug. 12 online issue of Neurology.

Risk factors associated with the development of neuropsychological deficits included:

Multiple seizures, OR 1.96 (95% CI 1.46 to 3.31)

Use of antiepileptic drugs, OR 2.27 (95% CI 1.35 to 3.84)

Symptomatic/cryptogenic etiology, OR 2.15 (95% CI 1.29 to 3.56)

Epileptiform activity on an initial EEG, OR 1.90 (95% CI 1.15 to 3.12)

A child with all four risk factors was three times more likely than healthy siblings to exhibit deficits in language, processing speed, verbal memory and learning, and attention/executive/construction factors, the researchers said.

Although cognitive impairments are well recognized in children with epilepsy, the timing and frequency of neuropsychological abnormalities and risk factors associated with them have not been clearly established.

To address these concerns, Fastenau and colleagues undertook a community-based study in which they enrolled 282 children who'd had a first-recognized, unprovoked seizure within the preceding three months and whose IQ was at least 70 and 147 healthy siblings as controls.

All of the children underwent standardized, individually administered testing.

They found that 27.4% of children who'd had seizures had a neuropsychological deficit, compared with 18.2% of the siblings (P=0.04).

Children with seizures scored lower than siblings on all domains in the tests, but there were no differences between the groups in academic achievement.

Almost twice as many children with seizures had deficits in attention/executive/construction factors, verbal memory and learning, and language compared with their siblings (13.9% versus 7.7% for each).

On multivariate logistic regression analysis, only symptomatic/cryptogenic etiology was a risk factor for neuropsychological deficit (P<0.02).

Further analyses revealed that there were different risk profiles between the idiopathic and symptomatic/cryptogenic subgroups.

In the idiopathic subgroup, odds ratios were greater than 2 for recurrence (OR 2.1, 95% CI 0.69 to 6.7) and for epileptiform activity on EEG (OR 2.7, 95% CI 0.74 to 10), while in the symptomatic/cryptogenic subgroup the odds ratio was greater than 2 for the use of antiepileptic drugs (OR 2.5, 95% CI 0.97 to 6.2).

The use of antiepileptic drugs was associated with deficits in all domains, even in children with no previous seizures and without EEG abnormalities, highlighting the importance of monitoring for neuropsychological deficits in children taking these drugs, the investigators wrote.

The risk of neuropsychological deficit was most pronounced in children taking valproic acid (OR 2, 95% CI 0.89 to 4.48).

Epileptiform activity on initial EEG was linked to slowing of processing speed (P=0.004), and even after controlling for use of antiepileptic drugs, the relationship between epileptiform activity and processing speed remained.

The investigators therefore suggested that "initial EEG provides a biomarker for processing speed deficits, which can facilitate rapid identification of a neuropsychological function that is critical to cognitive development in childhood."

The lack of a negative impact on academic achievement for months after a first-recognized seizure, according to the investigators, suggests that "there might be a window during which educational interventions could prevent or minimize the long-term impact on educational attainment, and presumably upon vocational success as adults," they wrote.

In an accompanying editorial, David W. Loring, PhD, and Kimford J. Meador, MD, of Emory University in Atlanta, wrote that the study provides "strong evidence that neuropsychological impairment can be directly attributed to the underlying brain substrate giving rise to the child's epilepsy rather than a secondary effect from extended exposure to medical therapy or cumulative seizure effects."

The editorialists also emphasized that the study's findings offer a "compelling rationale" for neuropsychological testing of all children with newly diagnosed epilepsy, so that educational interventions can "lessen the long-term cognitive burden of this disease."

Several of the study investigators disclosed research support from the National Institutes of Health and receiving honoraria and holding stocks in pharmaceutical companies, and the principal investigator receives royalties for a neuropsychological test and manual.

The editorialists disclosed research support from the National Institutes of Health and from several pharmaceutical and device companies.

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